Whether somatic cell differentiation generally involves irreversible changes in the DNA or highly stabilized changes in the DNA and/or associated proteins that are potentially reversible has not yet been demonstrated. Since some specialized cells can be induced to synthesize new and different gene products and change cell phenotype, cell specialization does not necessarily involve irreversible genetic changes. Nuclear transplantation into amphibian oocytes provides the greatest capability for activating genes and revealing the genetic and developmental potential of nuclei from specialized cells. This application proposes to test the genetic and developmental potential of frog nuclei from three specialized cell types (erythrocytes, lymphocytes and erythroblasts) by serially transplanting the nuclei into frog oocytes. The extent of development attained by the matured oocytes will reflect the content and functional capacity of the genome from these specialized cells, and the degree to which their genomes can be activated. In addition, nuclear transplants stemming from lymphocyte nuclei will be assayed for specificity of antibody production to determine if irreversible genetic changes occur in the immunoglobulin gene. The ability to activate genes and induce changes in cell phenotype has significant implications for controlling biomedical problems, such as regeneration, aging and cancer.